Development of new methodology to the synthesis of symmetrical Biaryls
By Souseelya K Vedula
Faculty Mentor: Dr. Jin Jin
• Introduction• Applications of Biaryls• Results and Discussion• Experimental procedure• Reaction Mechanism• Conclusion• Future work• References
Introduction• Biaryl compounds
• Coupling mechanisms
• Palladium catalyst : Widely used due to its stability to reaction conditions and inertness.
Types of Palladium Catalysts
Homogenous Palladium Catalyst : Palladium is directly added to the reaction mixture which makes the
recovery of the catalyst difficult.
Heterogeneous Palladium Catalyst: Palladium catalyst is attached to a solid support which can be
removed after reaction and can be reused.
Types of Coupling Reactions
Kumada coupling
Buchwald- Hartwig
Hiyama coupling
Applications
• Pharmaceutical Industry- Bi aryl scaffold forms the core of many therapeutic classes such as antifungal, anti-inflammatory, anti rheumatic and
anticancer drugs.
Allocolchicin – tubulin polymerization inhibitor Rhazinilam – tubulin polymerization / depolymerization inhibitor
Baudoin, O., Cesario, M., Guenard, D. J.Org. Chem., 2002, 67, 1199-1207.
Applications
Biphenomycin- A novel peptide
• Agrochemicals • Polymers• Light emitting diodes
Carbonelle, A., Zhu, J. Org. Let., 2000, 2, 3477-3480
Results and Discussionaryl iodide
I
I
I
I
H3CO
I
H2N
I
NH2
I
N
I
TeNH2 NH2
Te
Te
Te
Te
H2N NH2
Te
N
Te
N
Te
H3CO OCH3
entry yieldb (%)
1
product
1a, 92
2 1b, 98
3 1c, 90
4 1e, 82
5 1f, 95
6 1g, 96
7 1h, 56
8 1j, 84
a Reaction conditions: aryl iodide (1 equiv.), Te0 (1 equiv.), KOH (2 equiv.), and DMSO (2 mL) stirred at 110 oC for 10 h under nitrogen. b Isolated yields.
Cl Cl Cl
Table 1: Synthesis of diaryl tellurides
Results and Discussion
Experimental procedure
ArI ArTeArTe0
KOH, DMSO110 oC, 10 h
Scheme 1: Synthesis of symmetrial diaryl telluride ArTeAr
ITe0
KOH, DMSO
1100C, 10H
Te
Experimental procedure
ArTeArPdCl2, Na2CO3
Ar-Ar AgOAc, MeOH, rt 2h
Scheme 2: Synthesis of symmetrical biaryls by detelluration
TePdCl2, Na2CO3
AgOAc,MeOH rt, 2h
Reaction Mechanism
ArTeAr
Ar-Ar
TeAr
ArTe
Ar
ArPd (II)
Te PdAr
Ar
Scheme 3: Proposed mechanism for the formation of symmetrical biaryls
Pd (0) + Te (0) +
Ag+
Pd (II) Pd(0)
Conclusion
• In our research , a new method to synthesize symmetrical bi aryls has been developed by detelluration reaction of symmetrical diaryl tellurides.
• Many biaryls with different functional groups have been synthesized using this new technique.
• The new method to generate the biaryls will lead to more benign alternatives in the field of pharmaceuticals in the synthesis of bi aryl containing drugs.
Future work
• To synthesize more biaryl compounds of different substituents.
• To explore more aspects of organotellurium chemistry.
References• Shin-ichi, K., Puneet, S., Lars, E. Tetrahedron Letters, 2011, 52, 4120-4122.
• Baudoin, O., Cesario, M., Guenard, D. J.Org. Chem., 2002, 67, 1199-1207.
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Acknowledgement
• Dr. Jin Jin and Dr. Shaozhang Zang• Department of Chemistry• Western Illinois University• Family and Friends
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